Global and Regional Estimates for Subtype-Specific Therapeutic and Prophylactic HIV-1 Vaccines: A Modeling Study

Abstract

Global HIV-1 genetic diversity forms a major obstacle to the development of an HIV vaccine. It may be necessary to employ subtype-specific HIV-1 vaccines in individual countries according to their HIV-1 subtype distribution. We estimated the global and regional need for subtype-specific HIV-1 vaccines. We took into account the proportions of different HIV-1 variants circulating in each country, the genetic composition of HIV-1 recombinants, and the different genome segments (gag, pol, env) that may be incorporated into vaccines. We modeled different scenarios according to whether countries would employ subtype-specific HIV-1 vaccines against (1) the most common subtype; (2) subtypes contributing more than 5% of HIV infections; or (3) all circulating subtypes. For therapeutic vaccines targeting the most common HIV-1 subtype in each country, 16.5 million doses of subtype C vaccine were estimated globally, followed by subtypes A (14.3 million) and B (4.2 million). A vaccine based on env required 2.6 million subtype E doses, and a vaccine based on pol required 4.8 million subtype G doses. For prophylactic vaccines targeting the most common HIV-1 subtype in each country, 1.9 billion doses of subtype A vaccine were estimated globally, followed by subtype C (1.1 billion) and subtype B (1.0 billion). A vaccine based on env required 1.2 billion subtype E doses, and a vaccine based on pol required 0.3 billion subtype G doses. If subtype-specific HIV-1 vaccines are also directed against less common subtypes in each country, vaccines targeting subtypes D, F, H, and K are also needed and would require up to five times more vaccine doses in total. We conclude that to provide global coverage, subtype-specific HIV-1 vaccines need to be directed against subtypes A, B, and C. Vaccines targeting env also need to include subtype E and those targeting pol need to include subtype G.

Keywords: CRF; HIV; URF; recombinant; subtype; vaccine.

FIGURE 1

Global distribution of HIV-1 variants before and after reassignment of CRFs to “pure” HIV-1 subtypes. (A) Global proportions of HIV-1 subtypes A–K, CRF01_AE, CRF02_AG, other CRFs and URFs, based on most recent data available for each country. (B–E) Global proportions of HIV-1 variants after reassignment of CRFs to “pure” HIV-1 subtypes, based on full-length sequence (B), gag (C), pol (D), and env (E). CRF, circulating recombinant form; URF, unique recombinant form. Data underlying this figure is displayed in Supplementary Material, pp. 8–10.

FIGURE 2

Regional distribution of HIV-1 subtypes after reassignment of CRFs to “pure” HIV-1 subtypes. Regional proportions of HIV-1 subtypes after reassignment of CRFs to “pure” HIV-1 subtypes, based on full-length sequence (A), gag (B), pol (C), and env (D). We grouped all countries into 14 regions, as previously described (Hemelaar et al., 2019). Individual regions are shaded differently on the world map. The proportion of HIV infections attributed to each subtype in each region is shown in pie charts superimposed onto the regions. The sizes (surface area) of the pie charts for each region are proportional to the relative number of people living with HIV in each region. URF, unique recombinant form. Data underlying this figure is displayed in Supplementary Material, pp. 8–10.

FIGURE 3

Global estimates of the number of doses of subtype-specific therapeutic and prophylactic HIV-1 vaccines. Estimates of the number of doses of subtype-specific therapeutic (A–D) and prophylactic (E–G) HIV-1 vaccines. Estimates are stratified according to genome region (gag, pol, env, and full length) and the number of subtypes against which people in each country are vaccinated, according to different scenarios, i.e., vaccinating people against the most common subtype in each country (A,E), subtypes with a prevalence of >5% in people living with HIV in each country (B,F), all subtypes circulating in each country (C,G), and the HIV-1 subtype with which HIV-positive people are infected (D). Data underlying this figure is displayed in Table 1.

FIGURE 4

Regional estimates of the number of doses of subtype-specific therapeutic and prophylactic HIV-1 vaccines. Regional estimates for therapeutic (A) and prophylactic (B) HIV-1 vaccines based on the most common subtype, based on the full-length sequence, in each country. We grouped all countries into 14 regions, as previously described (Hemelaar et al., 2019). Individual regions are shaded differently on the world map. The estimates for vaccines based on each HIV-1 subtype are shown in pie charts superimposed onto the regions. The sizes of the pie charts (surface area) correspond to the relative number of vaccine doses for each region and the total number of vaccine doses is shown below each pie chart. mil, million. Data underlying this figure is displayed in Supplementary Material, p. 11.